Proconvulsant potential of cyproheptadine in experimental animal models

In epileptic patients cyproheptadine is frequently prescribed as an appetite stimulant for the treatment of anorexia associated with anti-epileptic drugs and for the management of 'serotonin syndrome' in depressed epileptic patients. However, the study of serotonergic and histaminergic pathway shows that the decreased neurotransmission of serotonin and histamine in the brain reduces seizures threshold. Since, cyproheptadine interferes with these pathways via antagonizing subtypes of 5-HT(1/2) receptors and H(1) receptor, therefore the present study was undertaken to investigate its effect on seizures threshold, so as to substantiate its use in epileptics. In the present study convulsions were induced in mice by, maximum electroshock (MES), picrotoxin, and pentylenetetrazol (PTZ). Cyproheptadine (4 mg/kg, i.p.) was administered per se and along with clinically used anti-epileptic drugs (phenytoin 25 mg/kg, i.p. and diazepam 5 mg/kg, i.p.) in different groups of mice, onset and extent of convulsions in these groups were compared with that of vehicle control and anti-epileptics per se treated groups. Percentage mortality in all groups was also determined. Results depicted a significant increase in duration of tonic hind limb extension in MES and decrease in latency to clonic convulsions induced by PTZ and picrotoxin in cyproheptadine treated groups (per se and along with anti-epileptics), as compared to vehicle control and anti-epileptics per se treated groups respectively. Percentage mortality was also increased with cyproheptadine treatment. Therefore it is concluded that cyproheptadine pretreatment reduces threshold, increases severity of seizures and decreases the efficacy of clinically used anti-epileptic drugs in experimental animal models of convulsions.